Ahead of the low, an unstable air mass advected northward from the Gulf of Mexico, while a warm front positioned itself across Kentucky, southern Illinois, and south-central Missouri.
By 8:00 p.m. EST (01:00 UTC), the low had deepened somewhat and tracked generally eastward across north-central Illinois, yielding a pressure of 29.274 inHg (991.3 mb) at Louisville, Kentucky, an hour earlier.
As a result, numerous long-lived tornado families occurred in a triangular region from St. Louis, Missouri, eastward to Louisville and southward to Huntsville, Alabama.
One or more members of the family may have been the same as the Bird's Point tornado and touched down in Missouri, west of the Mississippi River, before entering Kentucky.
After passing through McCracken County, the tornado traversed the Ohio River as a waterspout to strike the opposite shore at Metropolis, Illinois.
Between Blackford and Dixon the tornado destroyed several dozen farms and miles of timberland; widespread F4 damage occurred in this area.
The most extensive damage occurred in a swath from the intersection of 34th Street and the Algonquin Parkway to the western half of the central business district, including Crescent Hill.
Throughout the path, wreckage caught fire, burning several people to death; century-old oaks and a water tower were downed; and iron railings were wrenched and snapped.
Before crossing the Ohio River into Indiana, the tornado destroyed a total of 766 buildings–including 532 residences, 32 manufacturers, 10 tobacco warehouses, seven rail depots, five churches, three schools, and two public halls–in Louisville, costing the city at least $2.5 million.